This project investigates the potential of a sperm antigen, PH-20, as an immunocontraceptive in male and female macaques. This project is the major mating trial of PH-20 immunized female cynomolgus macaques. Forty-four females have been monitored for urinary steroids to verify that ovarian cycles are normal during the past year. In the initial study, females were injected with purified PH-20 with Ribi or Titermax as the adjuvant. Unfortunately, serum titers did not reach desired levels in any of the animals. We are now pursuing PH-20 immunization with FruendUs adjuvant in a very small number of animals (n=4) to verify that this form of PH-20 will produce an antigenic response. We will also investigate the possibility of using cholera toxin as an antigen with PH-20. Once the protocol that results in high serum antibody titers is identified, we will proceed with the large mating study planned for this project. The protocol for the large study is as follows; prior to immunization, blood, cervical mucus and vaginal washes will be collected from all animals. Inititial immunizations and 2 boosts with PH-20 and the adjuvant will be performed and if serum titers indicate good antibody response then mating trials will begin. Before mating trials begin, post-immunization samples of reproductive tract fluids will be collected. Each female will be mated three times per cycle at about the time of ovulation, as determined prior to injection by the urinary steroid assays, with a proven-fertile male (a different male each month) for 6 months. If treated females are not pregnant at the end of the mating trial, additional samples of reproductive tract fluids will be collected and ovarian function will be monitored by urinary steroids. *KEY* Macaque, Sperm antigen, Immunocontraception